The proposed research will investigate the manner in which metabolic transformations of the prostaglandins are altered by certain pathophysiologic conditions and changes in physiologic state and will evaluate the significance of these alternations on lung function. The prostaglandin precursor, arachidonic acid (AA), is the substrate from which a variety of prostanoids, including endoperoxides, primary prostaglandins, thromboxanes and prostacyclin (PGI2), are formed. Recent studies in this laboratory have shown that AA and several of its prostanoid metabolities are highly active in the canine bronchopulmonary system under normal, resting conditions. The proposed studies will contrast the effects of exogenously administered AA and prostanoids on lung function under conditions where pulmonary physiology has been altered by estrogenic, androgenic and anti-inflammatory steroids, E. Coli endotoxin, pulmonary edema and changes in blood gases and pH. Lung function will be assessed in intact dogs through measurements of static and dynamic lung compliance, airway resistance, functional residual capacity, wasted ventilation, shunt fraction, pulmonary vascular resistance, pulmonary blood volume and pulmonary extravascular space. This model will take advantage of simultaneous measurement of airway and vascular parameters in order to evaluate the interaction of these two systems. In addition, an attempt will be made to identify changes in patterns of pulmonary synthesis of prostanoids from AA using radioisotopic and thin-layer chromatographic techniques. The proposed research will provide important information about the metabolic transformations of prostaglandins by the airways and lung vasculature under normal, resting conditions and under conditions where lung physiology is altered. This information will increase our understanding of the role of prostaglandins in lung disease and lead to the development of new therapeutic approaches to a number of diseases of the lung, such as "shock lung", pulmonary hypertension and chronic obstructive lung disease.